55 results on '"Seifter JL"'
Search Results
2. Mind the gap.
- Author
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Turchin A, Seifter JL, and Seely EW
- Published
- 2003
3. Anion-gap metabolic acidemia: case-based analyses.
- Author
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Seifter JL
- Subjects
- Anions, Humans, Acid-Base Equilibrium, Acidosis diagnosis, Acidosis etiology
- Abstract
Not all metabolic acidosis is associated with an elevated chloride replacing the low bicarbonate concentration. When other acids, usually non-Cl organic acids are introduced into the blood an "Anion Gap" metabolic acidosis exists. The serum anion gap is calculated as [Na+] - ([Cl
- ] + [HCO3 - ]) = Unmeasured anions - Unmeasured cations. The normal gap is mostly due to negatively charged albumin: (Normal range: 8-12 meq/l) as the unmeasured anions, since albumin is usually reported in grams per liter (not meq/l). For diagnostic purposes, calculating the serum anion gap allows determination of coexisting acid-base processes in a patient. Assuming a 1:1 fall in bicarbonate compared with rise in anion gap in a usual gap acidosis, one can compare the Δ anion Gap/ΔHCO3 - : Δ gap = observed anion gap - normal anion gap and the Δ HCO3 - = normal HCO3 - - observed HCO3 - . A ratio of 1 suggests a simple anion gap acidosis; if <1 a superimposed non-gap acidosis is lowering HCO3 - and if >1 a superimposed metabolic alkalosis is raising HCO3 - . Comparing the anion gap and osmolar gap can narrow the differential diagnosis to include toxic alcohol ingestions with acidic metabolites such as ethylene glycol and methanol. Not all metabolic acidosis is associated with an elevated chloride replacing the low bicarbonate concentration. When other acids, usually non-Cl organic acids are introduced into the blood an "Anion Gap" metabolic acidosis exists. This review will consider the generation of anion-gap acidoses through case discussions.- Published
- 2020
- Full Text
- View/download PDF
4. Noncirrhotic hyperammonemia after deceased donor kidney transplantation: A case report.
- Author
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Li GZ, Tio MC, Pak LM, Krier J, Seifter JL, Tullius SG, Riella LV, Malek SK, and Stergachis AB
- Subjects
- Aged, Female, Humans, Hyperammonemia drug therapy, Hyperammonemia etiology, Kidney Failure, Chronic pathology, Prognosis, Transplantation, Homologous, Death, Hyperammonemia diagnosis, Kidney Failure, Chronic surgery, Kidney Transplantation adverse effects, Tissue Donors supply & distribution
- Abstract
A 72-year-old woman with end-stage kidney disease due to recurrent urinary tract infections and obstructive uropathy of a solitary kidney presented to our hospital for renal transplantation. She underwent successful transplantation of a deceased donor allograft, but developed acute mental status deterioration on the fifth postoperative day. Her serum ammonia was found to be markedly elevated to 447 μmol/L in the setting of normal hepatic function. She was treated with emergent dialysis and empiric antibiotics targeting urea-splitting organisms, and ultimately made a full neurologic recovery with stable renal allograft function. Noncirrhotic hyperammonemia (NCH) is an exceedingly rare clinical entity but seems to have a predilection for patients who have undergone solid organ transplantation. This report emphasizes the importance of rapid diagnosis and initiation of treatment for NCH, which is associated with a high rate of mortality and irreversible neurological morbidity. We outline the successful workup and management approach for this patient., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2019
- Full Text
- View/download PDF
5. Body Fluid Compartments, Cell Membrane Ion Transport, Electrolyte Concentrations, and Acid-Base Balance.
- Author
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Seifter JL
- Subjects
- Animals, Humans, Water-Electrolyte Balance physiology, Acid-Base Equilibrium physiology, Body Fluid Compartments metabolism, Cell Membrane metabolism, Electrolytes metabolism, Ion Transport physiology
- Abstract
Measurements made in the blood, part of the extracellular compartment, are used in the clinical assessment of acid-base disorders; however, intracellular events determine much of the metabolic importance of these disorders. Intracellular and interstitial compartment acid-base balance is complex and varies in different tissues. This review considers the determination of extracellular pH in the context of ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment. A further consideration is the role of these membrane transporters in the generation of acid-base disorders and the associated disruption of electrolyte balance. This review suggests a process of internal and external balance for pH regulation similar to that of potassium, and considers the role of secretory gastrointestinal epithelia and renal epithelia with respect to normal pH homeostasis and clinical disorders. Electroneutrality of electrolytes in the extracellular fluid is a fundamental feature of reciprocal changes in Cl
- or non-Cl- anions and HCO3 - . Normal mechanisms for protecting cell pH and producing normal gastrointestinal and renal secretions in healthy states also may result in disease when abnormal. In a similar manner, organic anions such as ketoacid anions and lactate, normally transported as fuels between organs, result in acid-base disturbances in disease. Understanding the genomic basis of these transporters may contribute to specific treatments., (Copyright © 2019. Published by Elsevier Inc.)- Published
- 2019
- Full Text
- View/download PDF
6. Introduction: New Perspectives in Acid-Base Regulation.
- Author
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Seifter JL
- Subjects
- Humans, Acid-Base Equilibrium physiology, Acid-Base Imbalance physiopathology, Homeostasis physiology, Kidney Diseases physiopathology
- Published
- 2019
- Full Text
- View/download PDF
7. Extracellular Acid-Base Balance and Ion Transport Between Body Fluid Compartments.
- Author
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Seifter JL and Chang HY
- Subjects
- Homeostasis physiology, Humans, Hydrogen-Ion Concentration, Water-Electrolyte Balance physiology, Acid-Base Equilibrium physiology, Body Fluid Compartments physiology, Ion Transport physiology
- Abstract
Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of these disorders concerns intracellular events. Intracellular and interstitial compartment acid-base balance is complex and heterogeneous. This review considers the determinants of the extracellular fluid pH related to the ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment. The generation of acid-base disorders and the associated disruption of electrolyte balance are considered in the context of these membrane transporters. This review suggests a process of internal and external balance for pH regulation, similar to that of potassium. The role of secretory gastrointestinal epithelia and renal epithelia with respect to normal pH homeostasis and clinical disorders are considered. Electroneutrality of electrolytes in the ECF is discussed in the context of reciprocal changes in Cl
- or non Cl- anions and [Formula: see text]., (Copyright © 2017 the American Physiological Society.)- Published
- 2017
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- View/download PDF
8. Disorders of Acid-Base Balance: New Perspectives.
- Author
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Seifter JL and Chang HY
- Abstract
Background: Disorders of acid-base involve the complex interplay of many organ systems including brain, lungs, kidney, and liver. Compensations for acid-base disturbances within the brain are more complete, while limitations of compensations are more apparent for most systemic disorders. However, some of the limitations on compensations are necessary to survival, in that preservation of oxygenation, energy balance, cognition, electrolyte, and fluid balance are connected mechanistically., Summary: This review aims to give new and comprehensive perspective on understanding acid-base balance and identifying associated disorders. All metabolic acid-base disorders can be approached in the context of the relative losses or gains of electrolytes or a change in the anion gap in body fluids. Acid-base and electrolyte balance are connected not only at the cellular level but also in daily clinical practice. Urine chemistry is essential to understanding electrolyte excretion and renal compensations., Key Messages: Many constructs are helpful to understand acid-base, but these models are not mutually exclusive. Electroneutrality and the close interconnection between electrolyte and acid-base balance are important concepts to apply in acid-base diagnoses. All models have complexity and shortcuts that can help in practice. There is no reason to dismiss any of the present constructs, and there is benefit in a combined approach.
- Published
- 2017
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9. INTERACTIVE MEDICAL CASE. Tracing the Cause of Abdominal Pain.
- Author
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Nayor J, Vaidya A, Srivastava A, Seifter JL, and Rutherford AE
- Subjects
- Biopsy, Ceruloplasmin analysis, Chelating Agents therapeutic use, Copper analysis, Copper metabolism, Copper urine, Fanconi Syndrome etiology, Female, Gallbladder diagnostic imaging, Gallbladder pathology, Hepatolenticular Degeneration complications, Hepatolenticular Degeneration drug therapy, Humans, Liver chemistry, Spleen diagnostic imaging, Transaminases blood, Trientine therapeutic use, Ultrasonography, Young Adult, Abdominal Pain etiology, Fanconi Syndrome diagnosis, Hepatolenticular Degeneration diagnosis, Liver pathology
- Published
- 2016
- Full Text
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10. Maintenance Intravenous Fluids in Acutely Ill Patients.
- Author
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Seifter JL
- Subjects
- Female, Humans, Male, Fluid Therapy, Hyponatremia therapy
- Published
- 2016
- Full Text
- View/download PDF
11. Nutritional Management of Kidney Stones (Nephrolithiasis).
- Author
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Han H, Segal AM, Seifter JL, and Dwyer JT
- Abstract
The incidence of kidney stones is common in the United States and treatments for them are very costly. This review article provides information about epidemiology, mechanism, diagnosis, and pathophysiology of kidney stone formation, and methods for the evaluation of stone risks for new and follow-up patients. Adequate evaluation and management can prevent recurrence of stones. Kidney stone prevention should be individualized in both its medical and dietary management, keeping in mind the specific risks involved for each type of stones. Recognition of these risk factors and development of long-term management strategies for dealing with them are the most effective ways to prevent recurrence of kidney stones.
- Published
- 2015
- Full Text
- View/download PDF
12. Medical student membership on a hospital-based institutional review board: a unique educational opportunity.
- Author
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Gromski MA, Miller CA, and Seifter JL
- Subjects
- Humans, United States, Committee Membership, Ethics Committees, Research organization & administration, Students, Medical
- Published
- 2015
- Full Text
- View/download PDF
13. Integration of acid-base and electrolyte disorders.
- Author
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Seifter JL
- Subjects
- Female, Humans, Male, Acid-Base Equilibrium physiology, Acid-Base Imbalance diagnosis, Bicarbonates metabolism
- Published
- 2015
- Full Text
- View/download PDF
14. Association of loop diuretic use with higher parathyroid hormone levels in patients with normal renal function.
- Author
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Corapi KM, McMahon GM, Wenger JB, Seifter JL, and Bhan I
- Subjects
- Adult, Age Factors, Aged, Body Mass Index, Female, Heart Failure drug therapy, Humans, Male, Middle Aged, Sex Factors, Parathyroid Hormone blood, Sodium Potassium Chloride Symporter Inhibitors therapeutic use
- Published
- 2015
- Full Text
- View/download PDF
15. Urinary creatinine-splitting bacteria after ileal-loop diversion causing underestimate of glomerular filtration rate.
- Author
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Seifter JL
- Subjects
- Cystectomy methods, Humans, Ileum surgery, Inulin, Male, Middle Aged, Quadriplegia complications, Urinary Bladder, Neurogenic etiology, Urinary Diversion methods, Amidohydrolases urine, Bacteriuria microbiology, Corynebacterium enzymology, Creatinine urine, Glomerular Filtration Rate, Ileum microbiology, Urinary Bladder, Neurogenic surgery
- Published
- 2014
- Full Text
- View/download PDF
16. Integration of acid-base and electrolyte disorders.
- Author
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Seifter JL
- Subjects
- Acid-Base Imbalance metabolism, Adult, Aged, Electrolytes metabolism, Female, Humans, Hydrogen-Ion Concentration, Ions metabolism, Male, Models, Chemical, Acid-Base Equilibrium physiology, Acid-Base Imbalance diagnosis, Bicarbonates metabolism
- Published
- 2014
- Full Text
- View/download PDF
17. Hypokalemia, its contributing factors and renal outcomes in patients with chronic kidney disease.
- Author
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Wang HH, Hung CC, Hwang DY, Kuo MC, Chiu YW, Chang JM, Tsai JC, Hwang SJ, Seifter JL, and Chen HC
- Subjects
- Aged, C-Reactive Protein metabolism, Diuretics therapeutic use, Female, Glomerular Filtration Rate, Hemoglobins metabolism, Humans, Hypokalemia drug therapy, Hypokalemia metabolism, Hypokalemia pathology, Kidney drug effects, Kidney metabolism, Male, Middle Aged, Proportional Hazards Models, Renal Insufficiency, Chronic drug therapy, Renal Insufficiency, Chronic metabolism, Renal Insufficiency, Chronic pathology, Severity of Illness Index, Treatment Outcome, Hypokalemia complications, Kidney pathology, Renal Insufficiency, Chronic complications
- Abstract
Background: In the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated., Design Participants & Measurements: 2500 participants with CKD stage 1-4 in the Integrated CKD care program Kaohsiung for delaying Dialysis (ICKD) prospective observational study were analyzed and followed up for 2.7 years. Generalized additive model was fitted to determine the cutpoints and the U-shape association between sK and end-stage renal disease (ESRD). sK was classified into five groups with the cutpoints of 3.5, 4, 4.5 and 5 mEq/L. Cox proportional hazard regression models predicting the outcomes were used., Results: The mean age was 62.4 years, mean sK level was 4.2±0.5 mEq/L and average eGFR was 40.6 ml/min per 1.73 m(2). Female vs male, diuretic use vs. non-use, hypertension, higher eGFR, bicarbonate, CRP and hemoglobin levels significantly correlated with hypokalemia. In patients with lower sK, nephrotic range proteinuria, and hypoalbuminemia were more prevalent but the use of RAS (renin-angiotensin system) inhibitors was less frequent. Hypokalemia was significantly associated with ESRD with hazard ratios (HRs) of 1.82 (95% CI, 1.03-3.22) in sK <3.5mEq/L and 1.67 (95% CI,1.19-2.35) in sK = 3.5-4 mEq/L, respectively, compared with sK = 4.5-5 mEq/L. Hyperkalemia defined as sK >5 mEq/L conferred 1.6-fold (95% CI,1.09-2.34) increased risk of ESRD compared with sK = 4.5-5 mEq/L. Hypokalemia was also associated with rapid decline of renal function defined as eGFR slope below 20% of the distribution range., Conclusion: In conclusion, both hypokalemia and hyperkalemia are associated with increased risk of ESRD in CKD population. Hypokalemia is related to increased use of diuretics, decreased use of RAS blockade and malnutrition, all of which may impose additive deleterious effects on renal outcomes.
- Published
- 2013
- Full Text
- View/download PDF
18. Chloride-liberal fluids and intracellular acidosis.
- Author
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Leaf DE, McMahon GM, and Seifter JL
- Subjects
- Female, Humans, Male, Kidney Calculi epidemiology
- Published
- 2013
- Full Text
- View/download PDF
19. Challenges in the diagnostic and therapeutic approach to nephrolithiasis.
- Author
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McMahon GM and Seifter JL
- Subjects
- Citric Acid urine, Diet, Humans, Hydrogen-Ion Concentration, Hypercalciuria complications, Hyperoxaluria complications, Nephrolithiasis diagnosis, Risk Factors, Secondary Prevention, Uric Acid urine, Nephrolithiasis therapy, Nephrolithiasis urine
- Abstract
Purpose of Review: The incidence of renal stones is rising along with the costs and morbidity associated with this condition. With careful evaluation and management, the great majority of recurrent stones are preventable. The cornerstone of this evaluation remains the 24-h urine collection. This review details the physiological rationale for commonly requested urine studies and details how these results should guide therapy with special emphasis on recent advances in the understanding of risk factors for stone disease. Challenges associated with the complicated patient will be addressed., Recent Findings: Long-term follow-up and repeated evaluations are effective at preventing recurrent stones and increasing patient satisfaction. There is growing appreciation of the complexity of dietary risks for stone disease, and traditional risk-factors such as dietary oxalate must be reevaluated., Summary: The key to stone prevention is the individualization of therapy to specific patient risk factors with a recognition that these factors can change over time leading to a need for alterations in preventive therapies.
- Published
- 2012
- Full Text
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20. Illness and identity.
- Author
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Seifter JL
- Subjects
- Female, Granulomatosis with Polyangiitis complications, Humans, Kidney Diseases etiology, Nephrology, Career Choice, Identity Crisis, Sick Role
- Published
- 2011
- Full Text
- View/download PDF
21. Uremic encephalopathy and other brain disorders associated with renal failure.
- Author
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Seifter JL and Samuels MA
- Subjects
- Animals, Brain Diseases complications, Brain Diseases physiopathology, Brain Diseases therapy, Encephalitis complications, Encephalitis therapy, Humans, Renal Insufficiency complications, Renal Insufficiency therapy, Sleep Wake Disorders complications, Sleep Wake Disorders physiopathology, Sleep Wake Disorders therapy, Uremia complications, Uremia therapy, Encephalitis physiopathology, Renal Insufficiency physiopathology, Uremia physiopathology
- Abstract
Kidney failure is one of the leading causes of disability and death and one of the most disabling features of kidney failure and dialysis is encephalopathy. This is probably caused by the accumulation of uremic toxins. Other important causes are related to the underlying disorders that cause kidney failure, particularly hypertension. The clinical manifestations of uremic encephalopathy include mild confusional states to deep coma, often with associated movement disorders, such as asterixis. Most nephrologists consider cognitive impairment to be a major indication for the initiation of renal replacement therapy with dialysis with or without subsequent transplantation. Sleep disorders, including Ekbom's syndrome (restless legs syndrome) are also common in patients with kidney failure. Renal replacement therapies are also associated with particular neurologic complications including acute dialysis encephalopathy and chronic dialysis encephalopathy, formerly known as dialysis dementia. The treatments and prevention of each are discussed., (© Thieme Medical Publishers.)
- Published
- 2011
- Full Text
- View/download PDF
22. Encephalopathies caused by electrolyte disorders.
- Author
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Samuels MA and Seifter JL
- Subjects
- Acid-Base Imbalance complications, Animals, Humans, Inappropriate ADH Syndrome complications, Water-Electrolyte Balance physiology, Water-Electrolyte Imbalance complications, Encephalitis etiology, Hyperkalemia complications, Hypernatremia complications, Hypokalemia complications, Hyponatremia complications
- Abstract
Some of the most common reasons for metabolic neurologic disturbances in the setting of a general hospital are frequently encountered electrolyte and related osmolality disorders. Hyperosmolality is usually related to hypernatremia and/or hyperglycemia. Identifying the cause and carefully calculating the water deficit is crucial to appropriate management. Hyponatremia may be hypertonic, isotonic, or hypotonic. When hypotonic, it may be hypervolemic, euvolemic, or hypovolemic in nature. Determining the precise nature of the hyponatremia allows the clinician to focus the therapy appropriately. The rate of development of hyponatremia is crucial to safe and appropriate treatment. In acutely developing hyponatremia, hypertonic saline is required, whereas in slowly developing hyponatremia, water restriction and slow correction is required to avoid the syndrome of osmotic demyelination. Disorders of potassium metabolism are also common electrolyte disorders seen in the general hospital. Appropriate diagnosis and management of hyperkalemia and hypokalemia are also discussed., (© Thieme Medical Publishers.)
- Published
- 2011
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23. Consideration of extrarenal creatinine clearance in the measurement of renal function after bowel endoscopy.
- Author
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Seifter JL and Fuller AP
- Subjects
- Colon microbiology, Colonoscopy, Humans, Cathartics adverse effects, Colon drug effects, Creatinine metabolism, Glomerular Filtration Rate, Phosphates adverse effects
- Published
- 2008
- Full Text
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24. Multi-detector row CT urography of normal urinary collecting system: furosemide versus saline as adjunct to contrast medium.
- Author
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Silverman SG, Akbar SA, Mortele KJ, Tuncali K, Bhagwat JG, and Seifter JL
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Retrospective Studies, Urography methods, Contrast Media, Furosemide, Kidney Tubules, Collecting diagnostic imaging, Sodium Chloride, Tomography, X-Ray Computed methods
- Abstract
Purpose: To retrospectively evaluate whether intravenous furosemide, either alone or in addition to intravenous saline, improved depiction of the normal urinary collecting system at multi-detector row computed tomographic (CT) urography., Materials and Methods: Institutional review board approval for review of patient images and medical records was obtained; informed consent was not required for this HIPAA-compliant study. Excretory phase images from multi-detector row CT urography in 87 patients (44 women, 43 men; age range, 21-83 years; mean, 53 years) were reviewed. Examinations were performed with, in addition to intravenous contrast medium, 250 mL of intravenous normal saline alone (n = 35), both 250 mL of normal saline and 10 mg of intravenous furosemide (n = 26), or 10 mg of furosemide alone (n = 26). Three readers, blinded to the imaging technique used, individually assigned opacification scores to each of six urinary collecting system segments. Urinary distention was assessed by one reader by measuring transverse widths of the proximal, middle, and distal ureteral segments. Mean opacification scores for each segment and mean ureteral width measurements for each technique were compared by using the Student t test., Results: Mean opacification scores achieved with furosemide were significantly higher than those achieved with saline for the middle (P = .008) and distal (P < .001) ureteral segments. Similarly, mean ureteral widths were significantly higher with furosemide than with saline for the middle (P = .04) and distal segments (P = .01). There was no overall benefit of administering both saline and furosemide., Conclusion: To optimize opacification and distention of the normal urinary collecting system, contrast material-enhanced multi-detector row CT urography may be supplemented with intravenous furosemide alone., ((c) RSNA, 2006.)
- Published
- 2006
- Full Text
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25. Clinical problem-solving. Mind the gap.
- Author
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Turchin A, Seifter JL, and Seely EW
- Subjects
- Bilirubin blood, Blood Chemical Analysis methods, Diagnosis, Differential, Dyspnea etiology, Female, Humans, Hypercholesterolemia complications, Hypercholesterolemia diagnosis, Hyponatremia diagnosis, Hypothyroidism complications, Hypothyroidism diagnosis, Inappropriate ADH Syndrome complications, Lipids blood, Liver Function Tests, Lung Diseases diagnosis, Middle Aged, Osmolar Concentration, Sodium blood, Hyponatremia etiology, Inappropriate ADH Syndrome diagnosis, Lung Diseases complications
- Published
- 2003
- Full Text
- View/download PDF
26. Myoglobinemia after CT-guided radiofrequency ablation of a hepatic metastasis.
- Author
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Shankar S, Tuncali K, vanSonnenberg E, Seifter JL, and Silverman SG
- Subjects
- Adenocarcinoma diagnostic imaging, Aged, Aged, 80 and over, Catheter Ablation methods, Humans, Liver Neoplasms diagnostic imaging, Male, Muscular Diseases blood, Muscular Diseases etiology, Adenocarcinoma secondary, Adenocarcinoma surgery, Catheter Ablation adverse effects, Liver Neoplasms secondary, Liver Neoplasms surgery, Myoglobin blood, Tomography, X-Ray Computed
- Published
- 2002
- Full Text
- View/download PDF
27. A "medical team" format for tutorial groups and cases.
- Author
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Lio PA, Martin SA, and Seifter JL
- Subjects
- Attitude of Health Personnel, Humans, Program Evaluation, Communication, Education, Medical, Undergraduate organization & administration, Endocrinology education, Group Processes, Interprofessional Relations, Nephrology education, Patient Care Team organization & administration, Students, Medical psychology
- Published
- 2001
- Full Text
- View/download PDF
28. An interactive, Web-based learning environment for pathophysiology.
- Author
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Parker MJ and Seifter JL
- Subjects
- Curriculum, Humans, Learning, Massachusetts, Organizational Objectives, Computer-Assisted Instruction methods, Education, Medical, Undergraduate organization & administration, Internet organization & administration, Multimedia, Physiology education, User-Computer Interface
- Published
- 2001
- Full Text
- View/download PDF
29. Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion.
- Author
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Lo JC, Chertow GM, Rennke H, and Seifter JL
- Subjects
- Adult, Fanconi Syndrome pathology, Female, Herpes Simplex prevention & control, Humans, Kidney ultrastructure, Lysine therapeutic use, Nephritis, Interstitial pathology, Fanconi Syndrome chemically induced, Lysine poisoning, Nephritis, Interstitial chemically induced
- Abstract
We report a case of a 44-year-old woman who developed Fanconi's syndrome in association with the oral ingestion of L-lysine. L-lysine is widely available in health food stores and has been recommended in the lay press for the treatment and prevention of recurrent herpes simplex. The development of a severe tubulointerstitial nephritis, and eventual progression to chronic renal failure, underscores the importance of this entity, heretofore unrecognized in humans.
- Published
- 1996
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30. Trimethoprim-sulfamethoxazole and hypouricemia.
- Author
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Chertow GM, Seifter JL, Christiansen CL, and O'Donnell WJ
- Subjects
- AIDS-Related Opportunistic Infections blood, Adult, Anti-Infective Agents administration & dosage, Case-Control Studies, Cohort Studies, Female, Hodgkin Disease complications, Humans, Male, Pneumonia, Pneumocystis blood, Pneumonia, Pneumocystis complications, Risk Factors, Time Factors, Trimethoprim, Sulfamethoxazole Drug Combination administration & dosage, AIDS-Related Opportunistic Infections drug therapy, Anti-Infective Agents adverse effects, Pneumonia, Pneumocystis drug therapy, Trimethoprim, Sulfamethoxazole Drug Combination adverse effects, Uric Acid blood
- Abstract
Background: Hypouricemia has been reported in a substantial fraction of patients with AIDS and attributed to an HIV-related renal urate transport defect. We tested the alternative hypothesis that hypouricemia was associated with the administration of high-dose trimethoprim-sulfamethoxazole (TMP-SMX)., Methods: Sociodemographic, clinical, and repeated laboratory data on 45 hospitalized patients with Pneumocystis carinii pneumonia (PCP) with and without HIV infection, were abstracted by a blinded reviewer. The primary outcome of interest was the percent change in serum uric acid concentration from baseline to hospital day 5 +/- 1., Results: Subjects who received TMP-SMX were older (mean age 44.8 vs. 37.0, p = 0.02), less likely to be HIV-seropositive (61% vs. 94%, p = 0.01), and more likely to have received glucocorticoid therapy (75% vs. 35%, p = 0.01) than those who received pentamidine, dapsone-trimethoprim, clindamycin-primaquine, sulfadiazine-pyramethamine, or a combination of these agents. The administration of TMP-SMX was associated with a 37% +/- 12% reduction in serum uric acid concentration, adjusting for the effects of age, sex, race, HIV antibody status, renal function, serum sodium, and the use of diuretics and glucocorticoids (p = 0.005)., Conclusion: Among a diverse cohort of hospitalized patients with PCP, treatment with high-dose TMP-SMX was strongly associated with a reduction in serum uric acid concentration over time.
- Published
- 1996
31. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study.
- Author
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Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, King AJ, Klahr S, Massry SG, and Seifter JL
- Subjects
- Adolescent, Adult, Aged, Antihypertensive Agents therapeutic use, Chronic Disease, Disease Progression, Female, Follow-Up Studies, Glomerular Filtration Rate physiology, Humans, Hypertension physiopathology, Kidney Diseases physiopathology, Kidney Diseases urine, Male, Middle Aged, Risk Factors, Hypertension prevention & control, Kidney Diseases diet therapy, Proteinuria complications
- Abstract
Objective: To examine the relations among proteinuria, prescribed and achieved blood pressure, and decline in glomerular filtration rate in the Modification of Diet in Renal Disease Study., Design: 2 randomized trials in patients with chronic renal diseases of diverse cause., Setting: 15 outpatient nephrology practices at university hospitals., Patients: 840 patients, of whom 585 were in study A (glomerular filtration rate, 25 to 55 mliters/min.1.73 m2) and 255 were in study B (glomerular filtration rate, 13 to 24 mliters/min.1.73 m2). Diabetic patients who required insulin were excluded., Interventions: Patients were randomly assigned to a usual blood pressure goal (target mean arterial pressure, < or = 107 mm Hg for patients < or = 60 years of age and < or = 113 mm Hg for patients > or = 61 years of age) or a low blood pressure goal (target mean arterial pressure, < or = 92 mm Hg for patients < or = 60 years of age and < or = 98 mm Hg for patients > or = 61 years of age)., Main Outcome Measures: Rate of decline in glomerular filtration rate and change in proteinuria during follow-up., Results: The low blood pressure goal had a greater beneficial effect in persons with higher baseline proteinuria in both study A (P = 0.02) and study B (P = 0.01). Glomerular filtration rate declined faster in patients with higher achieved blood pressure during follow-up in both study A (r = -0.20; P < 0.001) and study B (r = -0.34; P < 0.001), and these correlations were stronger in persons with higher baseline proteinuria (P < 0.001 in study A; P < 0.01 in study B). In study A, the association between decline in glomerular filtration rate and achieved follow-up blood pressure was nonlinear (P = 0.011) and was stronger at higher mean arterial pressure. In both studies, the low blood pressure goal significantly reduced proteinuria during the first 4 months after randomization. This, in turn, correlated with a slower subsequent decline in glomerular filtration rate., Conclusions: Our study supports the concept that proteinuria is an independent risk factor for the progression of renal disease. For patients with proteinuria of more than 1 g/d, we suggest a target blood pressure of less than 92 mm Hg (125/75 mm Hg). For patients with proteinuria of 0.25 to 1.0 g/d, a target mean arterial pressure of less than 98 mm Hg (about 130/80 mm Hg) may be advisable. The extent to which lowering blood pressure reduces proteinuria may be a measure of the effectiveness of this therapy in slowing the progression of renal disease.
- Published
- 1995
- Full Text
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32. Rapid release of bound glucose-6-phosphate dehydrogenase by growth factors. Correlation with increased enzymatic activity.
- Author
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Stanton RC, Seifter JL, Boxer DC, Zimmerman E, and Cantley LC
- Subjects
- Animals, Cells, Cultured, Cycloheximide pharmacology, Enzyme Activation, Guanine Nucleotides pharmacology, Inositol Phosphates pharmacology, Ionomycin pharmacology, Kidney Tubules, Proximal enzymology, Male, Pentose Phosphate Pathway, Pertussis Toxin, Phosphogluconate Dehydrogenase metabolism, Rats, Rats, Inbred Strains, Streptolysins, Tetradecanoylphorbol Acetate pharmacology, Virulence Factors, Bordetella pharmacology, Epidermal Growth Factor pharmacology, Glucosephosphate Dehydrogenase metabolism, Platelet-Derived Growth Factor pharmacology
- Abstract
Epidermal growth factor (EGF), a mitogen for renal proximal tubule cells, activated the hexose monophosphate (HMP) shunt in renal proximal tubule cells (Stanton, R. C., and Seifter, J. L. (1988) Am. J. Physiol. 254, C267-C271). We therefore evaluated the effect of EGF on the HMP shunt enzymes glucose 6-phosphate dehydrogenase (G6PD, the rate-limiting enzyme) and 6-phosphogluconate dehydrogenase. Rat renal cortical cells (RCC) were incubated with either EGF or platelet-derived growth factor (PDGF) and then assayed for G6PD and 6-phosphogluconate dehydrogenase activities. EGF and PDGF increased G6PD activity by 25 and 27% respectively. Although phorbol myristate acetate (PMA), ionomycin, PMA + ionomycin, and 8-bromo-cyclic AMP had no significant effect on the activity, a 5-min preincubation with PMA potentiated the activation of G6PD by PDGF. Growth factor activation of G6PD was also seen in a fibroblast and epithelial cell line. None of the agents affected 6-phosphogluconate dehydrogenase activity in the RCC or in the cell lines. Further exploration into a possible mechanism for G6PD activation revealed that growth factors caused release of G6PD from a structural element within the cell. Streptolysin O permeabilization of RCC did not cause significant release of G6PD. However, within 1 min of addition of EGF or PDGF to permeabilized cells, G6PD was released into the cell supernatant. The nonhydrolyzable analog of GTP, guanosine 5'-O-(thiotriphosphate), caused a similar release of G6PD. Preincubation with pertussis toxin or guanyl-5'-yl thiophosphate inhibited the PDGF but not the EGF effect. Although the data do not establish a definitive proof linking G6PD release and G6PD activation, these results suggest that they are related. Thus, growth factor stimulation of the HMP shunt likely occurs by a novel mechanism associated with release of bound G6PD.
- Published
- 1991
33. Nephrogenic diabetes insipidus responsive to indomethacin plus dDAVP.
- Author
-
Stasior DS, Kikeri D, Duel B, and Seifter JL
- Subjects
- Drug Therapy, Combination, Female, Humans, Middle Aged, Deamino Arginine Vasopressin administration & dosage, Diabetes Insipidus drug therapy, Indomethacin administration & dosage, Kidney Diseases complications
- Published
- 1991
- Full Text
- View/download PDF
34. Expression of Na(+)-H+ exchange and ATP-dependent proton extrusion in growing rat IMCD cells.
- Author
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Stanton RC, Boxer DC, and Seifter JL
- Subjects
- Amiloride pharmacology, Ammonium Chloride pharmacology, Animals, Cells, Cultured, DNA Replication, Ethylmaleimide pharmacology, Hydrogen-Ion Concentration, Kidney Medulla drug effects, Kinetics, Male, Proton-Translocating ATPases metabolism, Protons, Rats, Rats, Inbred Strains, Sodium-Hydrogen Exchangers, Thymidine metabolism, Adenosine Triphosphate metabolism, Carrier Proteins metabolism, Kidney Medulla metabolism, Sodium metabolism
- Abstract
As the last step of urinary acidification, the inner medullary collecting duct (IMCD) is thought to secrete protons into the tubular lumens by means of a H(+)-translocating adenosinetriphosphatase (H(+)-ATPase). However, recent studies have also shown the existence of Na(+)-H+ exchange activity in IMCD cells. Although the physiological function of the antiporter in IMCD cells is unknown, activation of Na(+)-H+ exchange in other cell-culture systems has been suggested to be closely associated with the process of cell growth. Thus presence of Na(+)-H+ exchange may relate to the growth phase of these cells. To examine intracellular pH (pHi) regulation in growing IMCD cells, we studied proton transport by Na(+)-dependent and Na(+)-independent mechanisms by microfluorimetry using the pHi-sensitive dye 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein acetoxymethyl ester (BCECF/AM). Actively growing cells, defined by [3H]thymidine incorporations, demonstrated an amiloride-sensitive Na(+)-dependent pHi recovery after an acid load. No pHi recovery was evident in the absence of Na+, indicating the importance of Na(+)-H+ exchange for pHi recovery. However, when evaluated in quiescent cells, Na(+)-dependent pHi recovery appeared to be diminished. Instead, a Na(+)-independent pHi recovery which was inhibitable by ATP depletion and by 1 mM N-ethylmaleimide was present, suggesting function of a H(+)-ATPase. These findings indicate that Na(+)-dependent proton extrusion activity (Na(+)-H+ exchange) but not Na(+)-independent proton extrusion activity is expressed during the rapid growth phase of IMCD cells, whereas the more quiescent cells express Na(+)-independent ATP-dependent proton extrusion activity and a possibly less active Na(+)-H+ exchanger.
- Published
- 1990
- Full Text
- View/download PDF
35. Cl- transport via anion exchange in Necturus renal microvillus membranes.
- Author
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Seifter JL and Aronson PS
- Subjects
- Amiloride pharmacology, Animals, Anions metabolism, Bicarbonates metabolism, Biological Transport, Chlorine, Diffusion, Electrophysiology, Hydrogen metabolism, Necturus, Potassium metabolism, Radioisotopes, Sodium metabolism, Valinomycin pharmacology, Chlorides metabolism, Kidney metabolism, Microvilli metabolism
- Abstract
We investigated the mechanism of Cl- transport in microvillus membrane vesicles isolated from Necturus kidneys. Cl- influx was insensitive to changes in membrane potential induced by K+ gradients and the K+ ionophore valinomycin, arguing against conductive Cl- transport. Inward gradients of Na+ or Na+ + K+ did not stimulate initial Cl- influx, arguing against direct Na+-Cl- or Na+-K+-Cl- cotransport. External Cl-, HCO3-, and NO3- each stimulated 36Cl efflux and inhibited 36Cl uptake, indicating anion exchange. Outward HCO3- gradients but not OH- gradients stimulated 36Cl influx, consistent with Cl- -HCO3- exchange. Cl- transport via anion exchange was inhibited by furosemide, bumetanide, and disulfonic stilbenes, but not by acetazolamide. External halides stimulated 36Cl efflux (Cl- = Br- greater than I- greater than F-) but the organic anions lactate, p-aminohippurate, and urate did not. Amiloride-sensitive Na+-H+ exchange was demonstrated. Finally, in the presence of a CO2/HCO3 buffer system, imposing an inward Na+ gradient caused a time-delayed stimulation of 36Cl uptake, consistent with indirect coupling of Na+-H+ and Cl- -HCO3- exchangers. We conclude that the parallel operation of Na+-H+ and Cl- -HCO3- exchangers rather than direct cotransport may account for the Na+-coupled uphill Cl- entry previously observed in the intact proximal tubular cell of Necturus.
- Published
- 1984
- Full Text
- View/download PDF
36. Atrial peptides inhibit oxygen consumption in kidney medullary collecting duct cells.
- Author
-
Zeidel ML, Seifter JL, Lear S, Brenner BM, and Silva P
- Subjects
- Amiloride pharmacology, Amphotericin B pharmacology, Animals, Dose-Response Relationship, Drug, Drug Interactions, Furosemide pharmacology, Humans, Kidney Medulla, Kidney Tubules, Collecting cytology, Kidney Tubules, Collecting enzymology, Osmolar Concentration, Rabbits, Sodium-Potassium-Exchanging ATPase metabolism, Atrial Natriuretic Factor pharmacology, Kidney Tubules metabolism, Kidney Tubules, Collecting metabolism, Oxygen Consumption drug effects
- Abstract
Atrial natriuretic peptides (ANP) stimulate renal Na+ excretion by poorly understood mechanisms, perhaps involving direct inhibition of Na+ transport in the kidney medulla. To examine the effects of ANP on renal cells directly, we prepared highly purified cell suspensions derived from inner and outer medullary collecting duct and thick ascending limb of rabbit kidney and monitored ouabain-sensitive oxygen consumption (QO2). Human ANP diminished QO2 by 27.4 +/- 1.6% (mean +/- SE) in inner medullary collecting duct cells but had no effect in cells derived from outer medullary collecting duct or thick ascending limb. The inhibitory effect of ANP was not additive with either amiloride or ouabain. ANP was without effect in the presence of amphotericin. These results indicate that ANP inhibited Na+ entry in inner medullary collecting duct cells. ANP-mediated inhibition of QO2 was dose dependent (Ki = 5.5 X 10(-10) M) and exhibited selectivity for peptide structure. These results suggest that atrial peptides enhance renal sodium excretion partly by direct inhibition of medullary collecting duct sodium transport.
- Published
- 1986
- Full Text
- View/download PDF
37. Sodium-hydrogen exchange and glucose transport in renal microvillus membrane vesicles from rats with diabetes mellitus.
- Author
-
Harris RC, Brenner BM, and Seifter JL
- Subjects
- Animals, Autoimmune Diseases metabolism, Biological Transport, In Vitro Techniques, Microvilli metabolism, Phlorhizin metabolism, Rats, Sodium-Hydrogen Exchangers, Temperature, Acid-Base Equilibrium, Carrier Proteins metabolism, Diabetes Mellitus, Experimental metabolism, Glucose metabolism, Kidney metabolism, Sodium metabolism
- Abstract
Diabetes mellitus is associated with important changes in renal hemodynamics and transport function. Disturbances in solute transport have also been characterized in nonrenal tissues during hyperglycemia and insulinopenia. The purpose of this study was to determine if diabetes is associated with adaptive changes in function of the brush-border membrane of the proximal tubule. We studied Na+ and glucose transport in rat microvillus membrane vesicles isolated from the renal cortex of streptozotocin-induced and BB/W autoimmune diabetic rats. Untreated diabetes was associated with an increase in pH-stimulated total and amiloride-sensitive 22Na+ uptake into vesicles. Insulin treatment returned vesicle 22Na+ uptake to control levels. The increased Na+/H+ exchange was shown to be a result of increased net renal acid production rather than a specific response to insulinopenia because treatment with NaHCO3 also returned 22Na+ uptake to control levels. On the other hand, Na+-glucose cotransport, which was depressed in vesicles from untreated diabetics, returned to control levels with insulin but not NaHCO3 administration. This decreased Na+-glucose cotransport was not secondary to reduction in transport sites in untreated diabetics. These results show that in diabetes mellitus, increased Na+/H+ exchange activity is not the direct result of insulinopenia. However, the diabetic state appears to alter the functioning of the luminal Na+-glucose cotransporter.
- Published
- 1986
- Full Text
- View/download PDF
38. Transport and metabolism in renal cells in culture.
- Author
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Stanton RC and Seifter JL
- Subjects
- Amino Acids metabolism, Animals, Biological Transport, Cells, Cultured, Glucose metabolism, Phosphates metabolism, Sodium metabolism, Kidney metabolism
- Published
- 1987
39. Intracellular pH regulation in rabbit renal medullary collecting duct cells. Role of chloride-bicarbonate exchange.
- Author
-
Zeidel ML, Silva P, and Seifter JL
- Subjects
- Acetazolamide pharmacology, Animals, Biological Transport drug effects, Carbon Dioxide metabolism, Hydrogen-Ion Concentration, In Vitro Techniques, Kinetics, Male, Potassium Cyanide pharmacology, Proton-Translocating ATPases antagonists & inhibitors, Rabbits, Stilbenes pharmacology, Bicarbonates metabolism, Chlorides metabolism, Kidney Medulla metabolism, Kidney Tubules metabolism, Kidney Tubules, Collecting metabolism
- Abstract
The renal medullary collecting duct (MCD) secretes protons into its lumen and HCO3 into its basolateral space. Basolateral HCO3 transport is thought to occur via Cl/HCO3 exchange. To further characterize this Cl/HCO3 exchange process, intracellular pH (pHi) regulation was monitored in freshly prepared rabbit outer MCD cells. Cells were separated by protease digestion and purified by Ficoll gradient centrifugation. pHi was estimated fluorometrically using the entrapped intracytoplasmic pH indicator, 6-carboxyfluorescein. Cells were preincubated in bicarbonate-containing solutions and then abruptly diluted into bicarbonate-free media. The MCD cell pHi response to abrupt removal of CO2/HCO3 included an initial alkalinization due to rapid CO2 efflux, followed by an acidification due to HCO3 efflux and a gradual recovery to the resting pHi of 7.24 +/- 0.06 partly due to the action of a plasma membrane H+-ATPase. The initial alkalinization required a CO2/HCO3 gradient and did not occur in the presence of acetazolamide. The acidification phase required intracellular HCO3 and extracellular Cl, which was consistent with a Cl/HCO3 exchange. MCD HCO3 efflux exhibited saturable kinetics for extracellular Cl, with a Michaelis constant (Km) of 29.9 +/- 7.7 mM. HCO3 efflux also exhibited preference for halides over NO3, SCN, and gluconate, and striking sensitivity to disulfonic stilbene and acetazolamide inhibition, with an apparent K1 of 5 X 10(-7) M for DIDS. The final pHi recovery required intracellular ATP, which indicated that Cl/HCO3 and H+-ATPase activities are present in the same cells in these suspensions. The results provide direct evidence for MCD Cl/HCO3 exchange and describe some of the properties of this transport process.
- Published
- 1986
- Full Text
- View/download PDF
40. Interactions between anion exchange and other membrane proteins in rabbit kidney medullary collecting duct cells.
- Author
-
Janoshazi A, Seifter JL, and Solomon AK
- Subjects
- 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid analogs & derivatives, 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid metabolism, 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid pharmacology, Animals, Anion Transport Proteins, Chlorides metabolism, Cytochalasins pharmacology, In Vitro Techniques, Kidney Tubules, Collecting cytology, Kinetics, Models, Biological, Ouabain pharmacology, Protein Binding drug effects, Rabbits, Spectrometry, Fluorescence, 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid analogs & derivatives, Carrier Proteins metabolism, Kidney Tubules metabolism, Kidney Tubules, Collecting metabolism, Membrane Proteins metabolism
- Abstract
In separated outer medullary collecting duct (MCD) cells, the time course of binding of the fluorescent stilbene anion exchange inhibitor, DBDS (4,4'-dibenzamido-2,2'-stilbene disulfonate), to the MCD cell analog of band 3, the red blood cell (rbc) anion exchange protein, can be measured by the stopped-flow method and the reaction time constant, tau TDBDS, can be used to report on the conformational state of the band 3 analog. In order to validate the method we have now shown that the ID50D,DBDS,MCD (0.5 +/- 0.1 microM) for the H2-DIDS (4,4'-diisothiocyano-2,2'-dihydrostilbene disulfonate) inhibition of tau DBDS is in agreement with the ID50,Cl-MCD (0.94 +/- 0.07 microM) for H2-DIDS inhibition of MCD cell Cl- flux, thus relating tau DBDS directly to anion exchange. The specific cardiac glycoside cation transport inhibitor, ouabain, not only modulates DBDS binding kinetics, but also increases the time constant for Cl- exchange by a factor of two, from tau Cl- = 0.30 +/- 0.02 sec to 0.56 +/- 0.06 sec (30 mM NaHCO3). The ID50,DBDS,MCD for the ouabain effect on DBDS binding kinetics is 0.003 +/- 0.001 microM, so that binding is about an order of magnitude tighter than that for inhibition of rbc K+ flux (KI,K+,rbc = 0.017 microM). These experiments indicate that the Na+,K+-ATPase, required to maintain cation gradients across the MCD cell membrane, is close enough to the band 3 analog that conformational information can be exchanged. Cytochalasin E (CE), which binds to the spectrin/actin complex in rbc and other cells. modulates DBDS binding kinetics with a physiological ID50,DBDS,MCD (0.076 +/- 0.005 microM); 2 microM CE also more than doubles the Cl- exchange time constant from 0.20 +/- 0.04 sec to 0.50 +/- 0.08 sec (30 mM NaHCO3). These experiments indicate that conformational information can also be exchanged between the MCD cell band 3 analog and the MCD cell cytoskeleton.
- Published
- 1989
- Full Text
- View/download PDF
41. Use of monoclonal antibodies to culture rat proximal tubule cells.
- Author
-
Stanton RC, Mendrick DL, Rennke HG, and Seifter JL
- Subjects
- Animals, Antigens immunology, Carrier Proteins metabolism, Cell Division, Cell Separation methods, Histocytochemistry, Kidney Tubules, Proximal immunology, Kidney Tubules, Proximal metabolism, Male, Mice, Mice, Inbred BALB C, Microscopy, Electron, Microvilli immunology, Rats, Rats, Inbred Strains, Sodium-Hydrogen Exchangers, Antibodies, Monoclonal, Kidney Tubules, Proximal cytology
- Abstract
Current renal cell culture techniques are limited by either a low yield of cells or by heterogeneity of cell types. We have used monoclonal antibodies to microvillus membrane proteins to isolate and culture a pure population of proximal tubule cells. The cells were characterized as proximal tubule cells by phase microscopy, enzyme histochemistry for alkaline phosphatase, butyrate esterase, and gamma-glutamyltransferase, electron microscopy, and specific reactivity with a variety of monoclonal antibodies for proximal tubule cells. Growth over 2-7 days yielded cell numbers up to 1,000-fold greater than obtained by single tubule microdissection. Dome formation was observed, suggesting intact fluid transport. In addition, Na+-H+ exchange and Na+-dependent D-hexose transport, known transport processes of the proximal tubule, were demonstrated by microfluorimetry of single cells and methyl-alpha-D-glucopyranoside uptake, respectively. Our results indicate that large numbers of homogeneous, cultured rat proximal tubule cells that maintain characteristics of in vivo proximal tubule cells can be obtained using a monoclonal antibody technique of isolation.
- Published
- 1986
- Full Text
- View/download PDF
42. Coupling of Na-H exchange and Na-K pump activity in cultured rat proximal tubule cells.
- Author
-
Harris RC, Seifter JL, and Lechene C
- Subjects
- Amiloride pharmacology, Ammonium Chloride pharmacology, Animals, Cells, Cultured, Hydrogen-Ion Concentration, Male, Ouabain pharmacology, Rats, Rats, Inbred Strains, Sodium-Hydrogen Exchangers, Carrier Proteins metabolism, Ion Channels metabolism, Kidney Tubules, Proximal metabolism, Potassium metabolism, Sodium metabolism
- Abstract
Na-H exchange was studied using electron probe analysis and microfluorescent pH analysis of individual cells, in 3-day primary cultures of rat proximal tubule cells (RPTC) obtained from 40- to 50-day-old Sprague-Dawley rats. After Na-K pump inhibition, the initial rate of net Na influx was inhibited 87% by 1 mM amiloride. K influx, an estimate of Na-K pump activity, was increased approximately three times in cells containing high Na (0.114 mM K X mM P-1 X min-1) compared with control cells containing low Na (0.038 mM K X mM P-1 X min-1). Single cell measurements of RPTC loaded with the cytoplasmic pH indicator 5- (and -6) carboxy-4',5'-dimethylfluorescein indicated that there was reversible intracellular acidification in the absence of external Na or in the presence of amiloride. When intracellular acidification was induced by the addition and subsequent removal of NH4Cl, recovery of intracellular pH was inhibited in the absence of external Na or in the presence of amiloride. Using a similar protocol, it was found that after intracellular acidification, the rate of Na influx increased at least 5.9 times, and intracellular Na content was increased 3.15 +/- 0.64 times at 60 s. There was an initial 50% inhibition of Na-K pump activity within the first 60 s compared with control (nonacidified) RPTC, secondarily followed by an increase in Na-K pump activity. Amiloride (0.5 mM) inhibited the acidification-induced increase in Na influx, and persistent acidification led to a persistent inhibition of Na-K pump activity compared with control. In summary, these results demonstrate that Na-H exchange mediates the majority of net Na influx into RPTC under our basal conditions and is necessary for maintenance of intracellular pH homeostasis. In RPTC, Na-H exchange is further activated by intracellular acidification, leading to a net increase in intracellular Na content, which secondarily stimulates Na-K pump activity. The initial inhibition of Na-K pump activity may be due to a direct effect of intracellular acidification.
- Published
- 1986
- Full Text
- View/download PDF
43. cGMP mediates effects of atrial peptides on medullary collecting duct cells.
- Author
-
Zeidel ML, Silva P, Brenner BM, and Seifter JL
- Subjects
- 1-Methyl-3-isobutylxanthine pharmacology, Animals, Cyclic GMP analogs & derivatives, Dose-Response Relationship, Drug, Microscopy, Electron, Nitroprusside pharmacology, Oxygen Consumption drug effects, Rabbits, Swine, Atrial Natriuretic Factor pharmacology, Cyclic GMP pharmacology, Kidney Tubules drug effects, Kidney Tubules, Collecting drug effects
- Abstract
Atrial natriuretic peptides (ANP) stimulate renal Na+ excretion by poorly understood mechanisms, possibly involving direct inhibition of Na+ transport in the renal medulla. We have previously shown that human ANP 4-28 (hANP) inhibits Na+ entry-dependent O2 consumption (QO2) in rabbit inner medullary collecting duct (IMCD) cells. Because ANP actions in other tissues appear to be mediated by guanosine 3',5'-cyclic monophosphate (cGMP), the present studies examined the role of cyclic nucleotides in IMCD cell responses to ANP. 8-Bromo-cGMP (8-BrcGMP) diminished QO2 by 23.5 +/- 1.2% (SE) in IMCD cells but had no effect in cells derived from outer medullary collecting duct (OMCD); dibutyryl-adenosine 3',5'-cyclic monophosphate (cAMP) was without effect in IMCD cells. The inhibitory effect of BrcGMP was not additive with ANP, amiloride, or ouabain. Amphotericin, which enhances Na+ entry into cells, prevented the inhibitory effect of 8-BrcGMP. These results indicate that 8-BrcGMP, like ANP, inhibited Na+ entry in IMCD cells. hANP stimulated a 10-fold increase in cGMP in IMCD cells without altering IMCD cAMP levels or OMCD cGMP levels. Isobutyl methylxanthine, which inhibits phosphodiesterase activity, enhanced both cGMP accumulation and inhibition of QO2 by submaximal levels (10(-9) M) of ANP. Nitroprusside raised cGMP levels in both IMCD and OMCD cells but inhibited QO2 only in IMCD cells. We conclude that cGMP mediates the transport effects of ANP in IMCD cells. Our results indicate that cGMP may play an important role in the regulation of sodium transport in renal epithelia.
- Published
- 1987
- Full Text
- View/download PDF
44. Atrial peptides inhibit Na+ entry-dependent oxygen consumption in rabbit inner medullary collecting duct cells.
- Author
-
Zeidel ML, Seifter JL, Brenner BM, and Silva P
- Subjects
- Animals, Biological Transport, Active drug effects, Cyclic GMP metabolism, In Vitro Techniques, Kidney Medulla drug effects, Kidney Medulla metabolism, Kidney Tubules, Collecting metabolism, Rabbits, Atrial Natriuretic Factor pharmacology, Kidney Tubules drug effects, Kidney Tubules, Collecting drug effects, Oxygen Consumption drug effects, Sodium metabolism
- Published
- 1986
45. Regulation of Na/H exchange in renal microvillus vesicles in chronic hypercapnia.
- Author
-
Zeidel ML and Seifter JL
- Subjects
- Acid-Base Imbalance metabolism, Acidosis metabolism, Acidosis, Respiratory metabolism, Alkalosis metabolism, Animals, Bicarbonates metabolism, Chronic Disease, Kidney Tubules, Proximal metabolism, Male, Microvilli metabolism, Rats, Rats, Inbred Strains, Hypercapnia metabolism, Kidney metabolism, Protons, Sodium metabolism
- Abstract
Several disturbances of acid-base balance, including chronic metabolic and respiratory acidoses and metabolic alkalosis, are associated with enhanced proximal tubule bicarbonate reabsorption. To determine whether augmented brush border Na/H exchange might mediate enhanced proximal tubule bicarbonate reabsorption in these disorders, we measured Na/H exchange activity in cortical brush border membrane vesicles (BBMV) prepared from rats and rabbits adapted to hypercapnia and other chronic acid-base disturbances. BBMV prepared from control animals and animals with chronic acid-base disturbances were similar as judged by marker enzymes, alkaline phosphatase, and ouabain-sensitive phosphatase. Despite profound respiratory acidosis, no increase in Na/H exchange activity could be detected in vesicles prepared from rats adapted to chronic (8 to 10 days) or subacute (24 hr) respiratory acidosis. In addition, vesicles prepared from rabbits exposed to chronic hypercapnia did not show increased Na/H exchange when compared with contemporaneous controls. By contrast, in agreement with previously published results, amiloride-sensitive sodium uptake was increased by 30% in vesicles derived from animals with ammonium chloride-induced acidosis compared with contemporaneous controls. Two models of chronic metabolic alkalosis were also studied; vesicles from alkalotic rats did not show any alteration in Na/H exchange. We conclude that metabolic acidosis, but not respiratory acidosis or metabolic alkalosis, leads to enhanced activity of the luminal Na/H exchanger.
- Published
- 1988
- Full Text
- View/download PDF
46. Intracellular pH regulation and proton transport by rabbit renal medullary collecting duct cells. Role of plasma membrane proton adenosine triphosphatase.
- Author
-
Zeidel ML, Silva P, and Seifter JL
- Subjects
- Acetates pharmacology, Acetic Acid, Adenosine Triphosphatases metabolism, Adenosine Triphosphate metabolism, Animals, Biological Transport, Active drug effects, Cell Membrane enzymology, Cell Membrane metabolism, Extracellular Space physiology, Hydrogen-Ion Concentration, Intracellular Fluid metabolism, Ion Channels metabolism, Kidney Medulla cytology, Kidney Medulla enzymology, Kidney Tubules, Collecting cytology, Kidney Tubules, Collecting enzymology, Male, Rabbits, Sodium physiology, Adenosine Triphosphatases physiology, Kidney Medulla metabolism, Kidney Tubules metabolism, Kidney Tubules, Collecting metabolism, Protons
- Abstract
Proton secretion in the renal medullary collecting duct is thought to occur via a luminal proton-ATPase. In order to determine what mechanism(s) participate in proton transport across medullary collecting duct (MCD) cells membranes, intracellular pH (pHi) regulation and proton extrusion rates were measured in freshly prepared suspensions of rabbit outer MCD cells. Cells were separated by protease digestion and purified by Ficoll gradient centrifugation. pHi was estimated fluorometrically using the entrapped intracytoplasmic pH indicator, 6-carboxyfluorescein. Proton extrusion rates were measured using a pH stat. The resting pHi of MCD cells was 7.19 +/- 0.05 (SE) in a nonbicarbonate medium of pH 7.30. When cells were acidified by exposure to acetate salts or by abrupt withdrawal of ammonium chloride, they exhibited pHi recovery to the resting pHi over a 5-min time-course. Depletion of greater than 95% of cellular ATP content by poisoning with KCN in the absence of glucose inhibited pHi recovery. ATP depletion inhibited proton extrusion from MCD cells. Treatment with N-ethylmaleimide also inhibited pHi recovery. In addition, cellular ATP content was dependent on transmembrane pH gradients, suggesting that proton extrusion stimulated ATP hydrolysis. Neither removal of extracellular sodium nor addition of amiloride inhibited pHi recovery. These results provide direct evidence that a plasma membrane proton-ATPase, but not a Na+/H+ exchanger, plays a role in proton transport and pHi regulation in rabbit MCD.
- Published
- 1986
- Full Text
- View/download PDF
47. Properties and physiologic roles of the plasma membrane sodium-hydrogen exchanger.
- Author
-
Seifter JL and Aronson PS
- Subjects
- Animals, Biological Transport, Active, Blood, Cell Division, Growth Substances physiology, Hydrogen metabolism, Hydrogen-Ion Concentration, Kinetics, Sodium metabolism, Sodium-Hydrogen Exchangers, Sodium-Potassium-Exchanging ATPase metabolism, Carrier Proteins physiology, Cell Membrane physiology
- Published
- 1986
- Full Text
- View/download PDF
48. Absence of Cl-OH exchange and NaCl cotransport in rabbit renal microvillus membrane vesicles.
- Author
-
Seifter JL, Knickelbein R, and Aronson PS
- Subjects
- 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid, 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid analogs & derivatives, 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid pharmacology, Acid-Base Equilibrium, Acridine Orange pharmacology, Animals, Bicarbonates metabolism, Hydrogen-Ion Concentration, Ion Channels drug effects, Kidney Cortex ultrastructure, Microvilli metabolism, Rabbits, Valinomycin pharmacology, Chlorides metabolism, Ion Channels metabolism, Kidney Cortex metabolism, Sodium Chloride metabolism
- Abstract
Cl-transport was studied in microvillus membrane vesicles isolated from the rabbit renal cortex. Inwardly directed K+ gradients in the presence of the K+ ionophore valinomycin (Val) enhanced 10 mM 36Cl uptake 2.5-fold, confirming a Cl- conductive pathway. An inwardly directed H+ gradient (pHin 7.5, pHout 6.0) stimulated 10 mM Cl- uptake 1.5-fold compared with pHin = pHout = 6.0. However, this H+ gradient stimulation of Cl- uptake appeared secondary to the H+ diffusion potential rather than to Cl-OH exchange, as it was abolished by Val and K+in = K+out. Additional evidence against Cl- transport via anion exchange was the failure of an inwardly directed Cl- gradient to generate an inside-acid pH gradient as monitored by quenching of acridine orange fluorescence. Cl- influx was the same in the presence of inwardly directed gradients of Na+, K+, Cs+, Li+, and Rb+, arguing against NaCl cotransport. Finally, conductive Cl- transport was reduced by the inhibitors furosemide, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid. These data indicate the presence of an inhibitor-sensitive, conductive mode of Cl- transport but fail to demonstrate significant pathways for Cl- OH exchange or NaCl cotransport in rabbit renal microvillus membrane vesicles.
- Published
- 1984
- Full Text
- View/download PDF
49. Radiation inactivation studies of renal brush border water and urea transport.
- Author
-
Verkman AS, Dix JA, Seifter JL, Skorecki KL, Jung CY, and Ausiello DA
- Subjects
- Acetamides metabolism, Animals, Biological Transport, Active radiation effects, Kidney Cortex ultrastructure, Kinetics, Mathematics, Microvilli metabolism, Microvilli radiation effects, Molecular Weight, Osmosis, Permeability, Rabbits, Thiourea metabolism, Body Water metabolism, Kidney Cortex radiation effects, Urea metabolism
- Abstract
Radiation inactivation was used to determine the nature and molecular weight of water and urea transport pathways in brush border membrane vesicles (BBMV) isolated from rabbit renal cortex. BBMV were frozen to -50 degrees C, irradiated with 1.5 MeV electrons, thawed, and assayed for transport or enzyme activity. The freezing process had no effect on enzyme or transport kinetics. BBMV alkaline phosphatase activity gave linear ln(activity) vs. radiation dose plots with a target size of 68 +/- 3 kDa, similar to previously reported values. Water and solute transport were measured using the stopped-flow light-scattering technique. The rates of acetamide and osmotic water transport did not depend on radiation dose (0-7 Mrad), suggesting that transport of these substances does not require a protein carrier. In contrast, urea and thiourea transport gave linear ln(activity) vs. dose curves with a target size of 125-150 kDa; 400 mM urea inhibited thiourea flux by -50% at 0 and 4.7 Mrad, showing that radiation does not affect inhibitor binding to surviving transporters. These studies suggest that BBMV urea transport requires a membrane protein, whereas osmotic water transport does not.
- Published
- 1985
- Full Text
- View/download PDF
50. Relation between the anion exchange protein in kidney medullary collecting duct cells and red cell band 3.
- Author
-
Janoshazi A, Ojcius DM, Kone B, Seifter JL, and Solomon AK
- Subjects
- Animals, Binding Sites, Biological Transport, Chromatography, Ion Exchange, Rabbits, Spectrometry, Fluorescence, Surface Properties, Anion Exchange Protein 1, Erythrocyte analysis, Erythrocyte Membrane analysis, Kidney Medulla analysis, Kidney Tubules analysis, Kidney Tubules, Collecting analysis, Membrane Proteins analysis
- Abstract
A membrane protein that is immunochemically similar to the red cell anion exchange protein, band 3, has been identified on the basolateral face of the outer medullary collecting duct (MCD) cells in rabbit kidney. In freshly prepared separated rabbit MCD cells, M.L. Zeidel, P. Silva and J.L. Seifter (J. Clin. Invest. 77:1682-1688, 1986) found that C1-/HCO-3 exchange was inhibited by the stilbene anion exchange inhibitor, DIDS (4,4'-diisothiocyano-2,2'-disulfonic stilbene), with a K1 similar to that for the red cell. We have measured the binding affinities of a fluorescent stilbene inhibitor, DBDS (4,4'-dibenzamido-2,2'-disulfonic stilbene), to MCD cells in 28.5 mM citrate and have characterized both a high-affinity site (Ks1 = 93 +/- 24 nM) and a lower affinity site (Ks2 = 430 +/- 260 nM), which are closely similar to values for the red cell of 110 +/- 51 nM for the high-affinity site and 980 +/- 200 nM for the lower affinity site (A.S. Verkman, J.A. Dix & A.K. Solomon, J. Gen. Physiol. 81:421-449, 1983). When Cl- replaces citrate in the buffer, the two sites collapse into a single one with Ks1 = 1500 +/- 400 nM, similar to the single Ks1 = 1200 +/- 200 nM in the red cell (J.A. Dix, A.S. Verkman & A.K. Solomon, J. Membrane Biol. 89:211-223, 1986). The kinetics of DBDS binding to MCD cells at 0.25 microM-1 are characterized by a fast process, tau = 0.14 +/- 0.03 sec, similar to tau = 0.12 +/- 0.03 sec in the red cell. These similarities show that the physical chemical characteristics of stilbene inhibitor binding to MCD cell 'band 3' closely resemble those for red cell band 3, which suggests that the molecular structure is highly conserved.
- Published
- 1988
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